Sulfated saccharides play important roles in many biological processes. For example, the sulfated Lea tetra- and pentasaccharides are potent E-selectin inhibitors and sialyl Lewis x with a sulfate group at the 6-position of galactose is a ligand for L-selectin. These sulfated sugars play important roles, among others, in cell adhesion in response to inflammatory reactions. The sulfation of hydroxysteroids provides hydrophilic forms for excretion. Many glycosaminoglycans [GAGs] are sulfated and are involved in numerous cellular functions. GAGs are long linear polysaccharides consisting of disaccharide repeats that contain an amino sugar and are found in most animals. Chondroitin [β(1,4)GlcUA-β(1,3)GalNAc]n and heparin/heparan [α1,4)GlcUA-[β(1,4)GlcNAc]n, (typically with an n=20 to 100) are sulfated at various positions. These GAGs play both structural and recognition roles on the cell surface and in the extracellular matrix.
In the course of oligosaccharide sulfation, 3-Phosphoadenylsulfate, also known as 3′-phosphoadenosine-5′-phosphosulfate (PAPS), is a substrate and cofactor for the enzymatic sulfation of oligosaccharides and steroids via sulfotransferases. Of the twenty-eight sulfotransferase enzymes [EC 2.8.2.1-28] listed in Enzyme Nomenclature 1992, E. C. Webb, ed., Academic Press, San Diego, Calif. 1992, pages 299-303, all but one enzyme utilize PAPS as the sulfate donor. Sulfotransferase activity varies with respect to the donor and/or acceptor compounds with which they work. Known sulfotransferases include those acting on carbohydrate: heparin/heparan sulfate N-sulfotransferase COST); chondroitin 6/keratan 6 sulfate sulfotransferase (C6ST/KSST); galactosylceramide 3′-sulfotransferase; heparan sulfate 2-sulfotransferase (Iduronic acid); HNK-1 sulfotransferase (3-glucuronic acid); heparan sulfate D-glucosamino 3-O-sulfotransferase (3-OST); etc., as well as those acting on phenols, steroids and xenobiotics: aryl sulfotransferase I & II, hydroxy-steroid sulfotransferases I, II & III, dehydroepiandrosterone (DHEA); etc.
The efficiency of oligosaccharide sulfation is limited by PAPS availability as a sulfate donor. PAPS synthesis has been reported, however, the synthesis procedures involve numerous steps with poor yields, which in turn limit the sulfated oligosaccharide product yield.
Despite numerous advances in the chemical synthesis of sulfated oligosaccharides and polysaccharides, to date, existing approaches are cumbersome, time-consuming and inefficient.